Efficacy of crizotinib in first-line treatment of adults with ALK-positive advanced NSCLC

Expert Opin Pharmacother. 2016 Aug;17(12):1693-701. doi: 10.1080/14656566.2016.1208171. Epub 2016 Jul 13.

Abstract

Introduction: The treatment of advanced non-small cell lung cancer (NSCLC) has evolved from palliative cytotoxic chemotherapy to precise medicine based on genetic alternations over the last decade. Anaplastic lymphoma kinase (ALK) rearrangement characterizes a molecular subset of NSCLC with an impressive response to crizotinib.

Areas covered: To analyze the efficacy of crizotinib in first-line treatment of adults with advanced ALK-positive NSCLC, updated data on development and recent advances of first-line crizotinib in this subset population are reviewed.

Expert opinion: To date, crizotinib should be established as a standard of care in previously untreated advanced NSCLC with ALK-rearrangement. However, the efficacy of first-line crizotinib is limited by acquired resistance. Second generation ALK inhibitors have demonstrated clinical activity in both crizotinib-refractory and crizotinib naïve setting. How to maximize first-line benefit for advanced ALK-positive NSCLC remains challenging. Combinational strategy, advances in companion diagnostics and optimization of ALK inhibitors might contribute to improve outcome in this subset of patients in future.

Keywords: ALK-positive; NSCLC; crizotinib; first-line treatment.

MeSH terms

  • Anaplastic Lymphoma Kinase
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Crizotinib
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Half-Life
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / mortality
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrazoles / pharmacokinetics
  • Pyrazoles / therapeutic use*
  • Pyridines / pharmacokinetics
  • Pyridines / therapeutic use*
  • Quality of Life
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Survival Rate

Substances

  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines
  • Crizotinib
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • ErbB Receptors
  • Receptor Protein-Tyrosine Kinases